Disposition of beta-methyldigoxin in man

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Clinical Pharmacology

Background:

• Beta-methyldigoxin is a cardiac glycoside used in treating heart conditions.
• Understanding its absorption, distribution, metabolism, and excretion (ADME) is crucial for effective therapeutic use.

Purpose of the Study:

• To investigate the pharmacokinetic profile of 3H-beta-methyldigoxin following oral and intravenous administration in healthy subjects.
• To determine the routes and extent of excretion and identify major metabolic pathways.

Main Methods:

• Single oral and intravenous doses of 3H-beta-methyldigoxin were administered to 12 healthy volunteers.
• Radioactivity in plasma, urine, and feces was measured over 7 days.
• Metabolites were analyzed to identify degradation and conjugation products.

Main Results:

• Nearly complete absorption of beta-methyldigoxin was observed when administered in solution.
• Excretion occurred primarily via urine (approx. 60%) and feces (approx. 30%) within 7 days.
• O-demethylation was the main metabolic pathway, with higher rates after oral administration. Polar conjugates, mainly mono- and bisglycosides, constituted up to 40% of plasma and urine radioactivity in the initial 12 hours.

Conclusions:

• Beta-methyldigoxin is well-absorbed orally and undergoes significant metabolism in humans, primarily through O-demethylation and conjugation.
• The pharmacokinetic behavior and metabolic profile differ slightly between oral and intravenous routes, impacting the proportion of unchanged drug excreted.